Modified Vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that cannot replicate in human cells. It is expected to have a better safety profile than the traditional smallpox vaccines. The IND for this study agent was submitted to the FDA in FY 02 and after IRB and FDA approval, the clinical study was initiated on 12/19/02. The clinical trial design is phase I/II, randomized, placebo-controlled, double-blinded, schedule-finding studies of MVA in healthy young adults who are vaccinia-naive. The hypothesis is that MVA will be safe in humans when administered by intramuscular (IM) injection and will result in an immune response comparable to that observed after Dryvax primary vaccination. Subjects were randomized to different primary immunization schedules either with Dryvax or with MVA or placebo. Each schedule includes a Dryvax challenge 12 weeks after completion of the primary vaccination schedule. Safety evaluations are performed on an ongoing basis throughout the study and immunogenicity samples are collected and frozen for batch testing by research laboratories. The Intramural Data and Safety Monitoring Board review interim safety data in June and December. The study was closed to accrual in June 2004 with 77 of the target 105 subjects enrolled.